title: Cellular sources and inducers of cytokines present in acute wound fluid.
abstract: Acute wounds contain many biological active molecules, including several cytokines and growth factors. However, the cellular sources of each molecule, as well as the stimuli inducing them, are poorly characterized. We quantified the levels of 27 cytokines, chemokines, and growth factors in acute wound fluid in a luminex-based assay. The acute wound fluid contained particularly high levels of IL-6 and IL-8, as well as elevated levels of MCP-1, IL-1RA, PDGF, IP-10, IFN-γ, and TNF-α. Surprisingly, the amounts of IL-1β and IL-10 were relatively low. To characterize the cellular sources of these molecules, we analyzed supernatants from monocytes, neutrophils, keratinocytes, fibroblasts, and endothelial cells stimulated with pro- and anti inflammatory cytokines, and different Toll-like receptor (TLR) ligands. The different cell types showed overlapping but distinct patterns of production of signal molecules, as well as sensitivity to ligands. Among pro-inflammatory cytokines, IL-1β was the most potent inducer of signal molecule production. Furthermore, keratinocytes and endothelial cells were in particular responsive to the Toll-like receptor-3 ligand poly I:C. New interactions between cytokines and growth factors were revealed, which may have important roles in wound healing, including IL-1β-induced IFN-γ and IL-10-induced VEGF.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. oystein.grimstad@ntnu.no
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Grimstad
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Sandanger
authors.forename: Liv
authors.initials: L
authors.lastname: Ryan
authors.forename: Kari
authors.initials: K
authors.lastname: Otterdal
authors.forename: Jan Kristian
authors.initials: JK
authors.lastname: Damaas
authors.forename: Brita
authors.initials: B
authors.lastname: Pukstad
authors.forename: Terje
authors.initials: T
authors.lastname: Espevik
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D018925:Chemokines / Q000032:analysis; D016207:Cytokines / Q000032:analysis*; D042783:Endothelial Cells / Q000378:metabolism; D005122:Exudates and Transudates / Q000737:chemistry*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology; D051193:Toll-Like Receptors / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D018925:Chemokines; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D051193:Toll-Like Receptors